CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-012705
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 MAP kinase-activated protein kinase 3 
Protein Synonyms/Alias
 MAPK-activated protein kinase 3; MAPKAP kinase 3; MAPKAP-K3; MAPKAPK-3; MK-3; Chromosome 3p kinase; 3pK 
Gene Name
 MAPKAPK3 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
80KLLYDSPKARQEVDHubiquitination[1]
184KEKDAVLKLTDFGFAubiquitination[2]
286QLIRLLLKTDPTERLubiquitination[1, 2]
Reference
 [1] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 
Functional Description
 Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, cell migration, chromatin remodeling and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38- alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. MAPKAPK2 and MAPKAPK3, share the same function and substrate specificity, but MAPKAPK3 kinase activity and level in protein expression are lower compared to MAPKAPK2. Phosphorylates HSP27/HSPB1, KRT18, KRT20, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins, such as TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. Also acts as a modulator of Polycomb-mediated repression. 
Sequence Annotation
 DOMAIN 44 304 Protein kinase.
 NP_BIND 50 58 ATP (By similarity).
 REGION 307 343 Autoinhibitory helix (By similarity).
 REGION 345 369 p38 MAPK-binding site (By similarity).
 MOTIF 335 344 Nuclear export signal (NES) (By
 MOTIF 350 353 Bipartite nuclear localization signal 1
 MOTIF 364 368 Bipartite nuclear localization signal 2
 ACT_SITE 166 166 Proton acceptor (By similarity).
 BINDING 73 73 ATP (By similarity).
 MOD_RES 1 1 N-acetylmethionine.
 MOD_RES 201 201 Phosphothreonine; by MAPK14 (By
 MOD_RES 251 251 Phosphoserine; by MAPK14 (By similarity).
 MOD_RES 307 307 Phosphoserine; by autocatalysis (By
 MOD_RES 313 313 Phosphothreonine; by MAPK14 (By  
Keyword
 3D-structure; Acetylation; ATP-binding; Complete proteome; Cytoplasm; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 382 AA 
Protein Sequence
MDGETAEEQG GPVPPPVAPG GPGLGGAPGG RREPKKYAVT DDYQLSKQVL GLGVNGKVLE 60
CFHRRTGQKC ALKLLYDSPK ARQEVDHHWQ ASGGPHIVCI LDVYENMHHG KRCLLIIMEC 120
MEGGELFSRI QERGDQAFTE REAAEIMRDI GTAIQFLHSH NIAHRDVKPE NLLYTSKEKD 180
AVLKLTDFGF AKETTQNALQ TPCYTPYYVA PEVLGPEKYD KSCDMWSLGV IMYILLCGFP 240
PFYSNTGQAI SPGMKRRIRL GQYGFPNPEW SEVSEDAKQL IRLLLKTDPT ERLTITQFMN 300
HPWINQSMVV PQTPLHTARV LQEDKDHWDE VKEEMTSALA TMRVDYDQVK IKDLKTSNNR 360
LLNKRRKKQA GSSSASQGCN NQ 382 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004708; F:MAP kinase kinase activity; TAS:ProtInc.
 GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0044351; P:macropinocytosis; ISS:UniProtKB.
 GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
 GO:0007265; P:Ras protein signal transduction; TAS:Reactome.
 GO:0032496; P:response to lipopolysaccharide; ISS:UniProtKB.
 GO:0051403; P:stress-activated MAPK cascade; TAS:Reactome.
 GO:0034166; P:toll-like receptor 10 signaling pathway; TAS:Reactome.
 GO:0034134; P:toll-like receptor 2 signaling pathway; TAS:Reactome.
 GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
 GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
 GO:0034146; P:toll-like receptor 5 signaling pathway; TAS:Reactome.
 GO:0034162; P:toll-like receptor 9 signaling pathway; TAS:Reactome.
 GO:0038123; P:toll-like receptor TLR1:TLR2 signaling pathway; TAS:Reactome.
 GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; TAS:Reactome.
 GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome. 
Interpro
 IPR011009; Kinase-like_dom.
 IPR027442; MAPKAPK_C.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 
Pfam
 PF00069; Pkinase 
SMART
 SM00220; S_TKc 
PROSITE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 
PRINTS